Linked Life Data

19095031

Source:http://linkedlifedata.com/resource/pubmed/id/19095031

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-1-22
pubmed:abstractText
Currently available treatments for rheumatoid arthritis (RA) are often ineffective in ameliorating the progression of disease, particularly the invasive destruction of articular cartilage and bone, and RA remains incurable. Therefore, vaccinotherapy of RA with an antigen-specific tolerizing DNA vaccine may offer new promise for overcoming this difficulty. Using recombinant technology, the DNA sequences encoding chicken type II collagen (CCOL2A1) with deleted N-propeptides were obtained from the plasmid pPIC9K/pCalpha(1)(II), and then cloned into pcDNA3.1(+). The resulting recombinant plasmid pcDNA-CCOL2A1 was produced in Escherichia coli, purified, characterized and used as a tolerizing DNA vaccine for the treatment of collagen-induced arthritis (CIA). Therapeutic efficacy and potential action mechanisms of pcDNA-CCOL2A1 tolerizing DNA vaccine against CIA were studied. Here we demonstrate that a single intravenous treatment with novel tolerizing DNA vaccine pcDNA-CCOL2A1 can induce potent immune tolerance against CIA. The efficacy of this therapy was verified by clinical visual scoring, radiographic X-ray, histopathological examination, and anti-CII IgG levels. Furthermore, the action mechanism behind this efficacy can be at least partially attributed to increased CD4(+)CD25(+) T regulatory cells, which specifically down-modulate the T lymphocyte proliferative response to CCII, induce a shift of Th1 to Th2 cells, as well as down-regulate Th1-cytokine TNF-alpha, while up-regulating both Th2-cytokine IL-10 and Th3-cytokine TGF-beta. More importantly, pcDNA-CCOL2A1 alone seems to be as effective as the current "golden standard" treatment, methotrexate (MTX). Taken together, these results suggest that we have successfully developed a novel tolerizing DNA vaccine encoding CCII, which is the first description of a tolerizing DNA vaccine encoding CCII for antigen-specific tolerizing therapy but not prophylactic against CIA.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0264-410X
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
690-700
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Construction and characterization of a novel DNA vaccine that is potent antigen-specific tolerizing therapy for experimental arthritis by increasing CD4+CD25+Treg cells and inducing Th1 to Th2 shift in both cells and cytokines.
pubmed:affiliation
Department of Immunology and National Center for Biomedicine Analysis, Beijing 307 Hospital Affiliated to Academy of Medical Sciences, No. 8 Dongda Ave., Fengtai District, Beijing 100071, PR China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't